CARDIORESPIRATORY PHARMACOLOGY

ASTHMA
ETTA C. CATACUTAN
MARCH 19, 2021

I. CLASSIFICATION OF ASTHMA
1. Intermittent • Nebulizers
• Least severe o Small machine to convert a drug solution into mist
• s/s: cough or wheezing – less than twice a week o Droplets in the mist are much finer than those produced
• Mgt: short-acting beta agonist (SABA) as needed by inhalers
2. Mild Persistent o Through face mask or mouth piece held between the
teeth
• s/s: more than twice per week, but less than once /day
o Take several minutes to deliver the amount of drug from
• s/s affect pt’s daily activity, sleep during night, nocturnal
a nebule
coughing, wheezing or dyspnea is experienced more
than twice /month
III. MEDICATIONS
• Mgt: ICS, SABA
3. Moderate Persistent
• s/s are experienced almost daily A. ANTIHISTAMINES
• Exacerbation of symptoms are experienced at least • H1 receptor antagonists
2x/wk, may persist for several days o Inhibit smooth muscle constriction in blood vessels &
• s/s affect pt’s daily activity, sleep during night, nocturnal respiratory & GI tracts
coughing, wheezing or dyspnea is experienced more o Decrease capillary permeability
than once/ week o Decrease salivation & tear formation
• Mgt: SABA, LABA, OCS, ICS daily • Used for variety of allergic disorders to prevent or reverse
4. Severe Persistent target organ inflammation
• Worst category H1 BLOCKER or H1 ANTAGONISTS
• s/s are experienced almost continually • Compete with histamine for receptor sites thus preventing
• Exacerbations are frequent and may last for weeks HISTAMINE RESPONSE
• s/s affect pt’s daily activity, sleep during night, nocturnal • Do not affect RELEASE of HISTAMINE but BLOCK action of
coughing, wheezing or dyspnea is experienced almost Histamine @ H1 Receptor Sites
every night • CONSTRICTION of extravascular smooth muscle lining the
• Mgt: daily SABA & ICS, LABA, OCS nasal cavity
• Prevents/reduces INCREASED CAPILLARY
PERMEABILITY
• ANTI-CHOLINERGIC EFFECTS: dry mouth; constipation;
blurred vision, urinary retention
• VASODILATION
Indications:
• treatment of nasal allergies, particularly seasonal allergic
rhinitis (Hay fever)
• Reduce rhinorrhea & sneezing but are usually less effective
for nasal congestion
• Are also used topically in the eye, in the nose, & on the skin

i. First-generation H1 receptor antagonists

• Non-selective/sedating
• Bind to both central & peripheral H1 receptors
• Usually cause CNS depression (drowsiness, sedation) but
may cause CNS stimulation (anxiety, agitation), especially in
children
• Also have substantial anticholinergic effects
II. INHALATION DEVICES
• Metered-dose Inhalers (MDIs) Examples:
o Pressurized devices that deliver a measured dose of Drug Dosage
drug with each activation Adult Child
o With CFC (Chlorofluorocarbon) or non-CFC Chorpheniramine 4 mg q4-6hr, max: 1-2yrs: 1 mg twice daily
propellant=force to generate the aerosol cloud (4 mg tablet, 24 mg daily 2-12yrs: 1- 2 mg q4-6h,
▪ (carbon, chlorine, fluorine) 2mg/ml Elixir & Max:12 mg daily
o Hand-mouth coordination is required expectorant)
o Spacers Hydroxyzine (25 25 mg at night; 6 months-6yrs: 5-15 mg
▪ Use with MDIs mg tablet) 25mg three to four daily; 50 mg daily in
▪ Increase delivery of drug to the lungs & decrease times daily when divided dose if needed
deposition of drug on the oropharyngeal mucosa necessary >6yrs: 15-25 mg daily;
▪ Especially important for inhaled corticosteroids 50-100 mg daily in
• Dry-powder Inhalers (DPIs) divided dose if needed
o Include Turbuhalers & Accuhalers Diphenhydramine 25-50 mg q4-6h 6.25-25 mg q4-8 hr ( >1
o Drugs are in the form of dry, micronized powder (10 mg/5ml Elixir) yr)
o Breath activated, much easier to use

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 Promethazine 25 mg at night; 25 2-10yrs: 5-25 mg daily • Void before each dose (urinary retention)
(10 & 25 mg mg twice daily if in 1 to 2 divided dose • Skin care (skin eruption & itching)
tablets, 5mg/5ml needed • Avoid overdosage
Elixir) • Avoid ROH
Azatadine (1 mg 1 mg twice daily 1-12 yrs: 0.25-1 mg • As prophylaxis of MOTION SICKNESS – take drug 30 mins
tablet) twice daily before event
• Small amount pass in BM; infant may develop unusual
Diphenhydramine (Benadryl) excitement or irritability
• Pharmacokinetics:
o [PO, IM, IV] well absorbed from the GIT B. BRONCHODILATORS
o Highly CHON bound
• Drugs used to relieve bronchospasms associated with
o Ave t ½ = 2-7 hrs
respiratory disorders
o Metabolized: liver
o Excreted: as metabolites in the urine • Includes:
o Adrenoceptor agonists
• Pharmacodynamics:
▪ Selective β2-agonists & other adrenoceptor
o ONSET of action-15 mins when taken orally
agonists
o DURATION of action: 4-8 hours
o Antimuscarinic/Anticholinergic bronchodilators
• MAJOR S/E: DROWSINESS
o Xanthine derivatives
• Used as sleep- aid product
• DRUGS that stimulate SNS = ADRENERGICS,
• Used also as ANTITUSSIVE (alleviates cough) ADRENERGIC AGONISTS, ADRENOCEPTORS,
• MAY cause CNS DEPRESSION: SYMPATHOMIMETICS
o If taken with alcohol, narcotics, hypnotics or • ACT on the adrenergic receptor sites in cells of SM =
barbiturates HEART, BRONCHIOLE WALLS, GIT, URINARY
• COMMON SE: BLADDER & CILIARY MUSCLES of the EYE
o Drowsiness, dizziness, fatigue, disturbed coordination
o Anticholinergic effects (dry mouth, urine retention, Four Main Receptors:
blurred vision) • Alpha 1 – INCREASE FORCE OF CONTRACTION,
vasoconstriction= HPN, mydriasis, decreased salivary
Hydroxyzine secretions, nasal decongestants
• Adverse effects: • Alpha 2 – inhibits release of NOREPINEPHRINE – dilates
o Sedation BV (anti HTN), decrease GI motility & tone
o Dry mouth
• Beta 1 – INCREASE HR & force of contraction, increase
o Blurred vision
RENIN= HPN
o GI disturbances
• Beta 2 – dilates bronchioles, GI and uterine relaxation,
o Headache
increase blood sugar, increase blood flow in the skeletal
o Urinary retention
muscles
• Hydroxyzine is not recommended for pregnancy & breast-
feeding
i. ADRENOCEPTOR AGONISTS
ii. Second-generation H1 Receptor Antagonists • Sympathomimetics/Adrenergic
• Selective beta2 agonists
• Selective/non-sedating
o Stimulate beta2 receptors in smooth muscle of the
• Cause less CNS depression because they are selective for
lung, promoting bronchodilation, and thereby relieving
peripheral H1 receptors & do not cross blood-brain barrier
bronchospasms
• Longer-acting compared to first-generation antihistamines o They are divided into short-acting & long-acting types
Drug Dosage Drug Formulation Dosage
Adult Child Short-acting β-2 agonists Adult Child
Acrivastine 8 mg three times Not recommended Oral Tablet 8 mg twice 4 mg twice daily
(Semprex) daily daily
Cetirizine (Zyrtec) 10 mg daily 5 mg daily / 2.5 mg Inhaler 100-200mcg Same as adult
twice daily (2-6 yrs) (MDI), 100 up to three
Desloratadine 5 mg daily 1.25 mg daily (2-5 yrs) Salbutamol mcg/dose to four times
(Aerius) 2.5 mg daily (6-11yrs) Nebulization daily
Fexofenadine 120-180 mg daily Not recommended Syrup, 4 mg three 1-2 mg three to
(Telfast) 2mg/5ml to four times four times daily
Loratadine 10 mg daily 5 mg daily (2-5 yrs) daily (≥2 yr)
(Claritine) Oral tablet 5-7.5 mg two -
(S.R) times daily
• Adverse effects: Inhaler 500 mcg up -
o May cause slight sedation 500mg/dose to four times
o Some antihistamines may interact with Terbutaline
(Turbuhaler) daily
▪ antifungal, e.g., ketoconazole Inhaler 250-500mcg Same as adult
▪ antibiotics, e.g., erythromycin 250mg/dose up to 3-4
▪ prokinetic drug – cisapride (MDI) times daily
Long-acting β-2 agonists
Special Consideration: Formoterol Inhaler
• To increase absorption = take the drug on EMPTY 4.5mg/dose
STOMACH, 1 hr ac or 2 hrs pc 4.5-9 mcg
(Turbuhaler)
• If GI upset is a problem – give with meals Inhaler
once or Same as adult
• IM – large muscle; avoid SQ 9mcg/dose
twice daily
• Provide sugarless candies/lozenges (due to dryness, (MDI)
nausea & anorexia)
• Increase HUMIDITY & push fluids
• Safety measures
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 Salmeterol Inhaler 50-100 mcg Same as adult Adverse Effects (Anticholinergic Bronchodilators)
25mcg/dose twice daily • Dry mouth
(MDI) • Nausea
50 mcg/dose 50 mcg twice Same as adult • Constipation
(Accuhaler) • Headache
• Palpitations
Albuterol (Ventolin/Proventil)
• more selective for beta 2 receptors = BRONCHODILATION iii. XANTHINE DERIVATIVES
with long duration of action
• Theophylline is a bronchodilator which relaxes smooth
Metaproterenol (Aluprent, Metaprel)
muscle of the bronchi, it is used for reversible airway
• has some beta 1 effect but is primarily as beta 2 agonist; obstruction
administered orally or with MDI or nebulizer
• MOA: mobilize calcium w/in the cells - stimulating
Isoproterenol (Isuprel)
prostaglandins= smooth muscle relaxation
• has no alpha- agonist properties, stimulates both beta 1 &
beta 2 receptors;
Drug Formulation Dosage
• Beta 1 receptors stimulated = HR increases, tachycardia Adult Child
• Beta 2 = bronchodilation Tablet 200/ 200 – 300 10 mg / kg
o Administered by inhalation using aerosol inhaler or 300 mg mg twice ((≥2yrs) twice
nebulizer (S.R.) daily daily
Adverse Effects
Capsule 7-12 mg/ kg 10-16 mg / kg /
• Tachycardia and palpitations 50/100 mg / day in two day in two
• Headache (slow divided divided doses
• Tremor, dizziness, nervousness release) doses (9–16yrs)
• increased BP, pulse rate & palpitations Theophylline 13-20 mg / kg /
• Blood glucose may increase day in two
divided doses
OTHER ADRENORECEPTOR AGONISTS (30 months – 8
• Less suitable & less safe for use as bronchodilators because yrs)
they are more likely to cause arrhythmias & other side effects Syrup 80 25 ml q8h 1 ml / kg (Max
Ephedrine mg/15 ml 25 ml) q6h
• Adults: 15-60 mg tid po (≥2yrs)
• Child: 7.5-30 mg tid po Injection 25 500 mg / kg 1 mg / kg /hr (6
Adrenaline (epinephrine) mg / ml / hr IV months – 9
• injection is used in the emergency treatment of acute allergic 10 ml infusion, years)
and anaphylactic reactions adjust when 800 mcg / kg /hr
Aminophylline
necessary (10 – 16 yrs)
Considerations: IV infusion,
• When 2 or more puffs are needed, inform the patient that at adjust when
least 1 minute should be allowed between puffs necessary
• Inform the patient that salmeterol and formoterol (long-
acting), and oral β-2 agonists should be taken on a fixed Adverse effects:
schedule, not on a prn basis • Toxicity is related to theophylline levels
• Instruct the patient to report chest pain and changes in heart (Therapeutic level =10-20 µg/ml)
rhythm or rate, because β-1 agonists can cause cardiac • 20-25 µg/ml: Nausea, vomiting, diarrhea, insomnia,
stimulation restlessness
• Contact physician if symptoms such as nervousness, • >30 µg/ml: Serious adverse effects including dysrhythmias,
insomnia, restlessness and tremor become severe convulsions, cardiovascular collapse which may result in
death
ii. ANTICHOLINERGIC BRONCHODILATOR Considerations:
Antimuscarinic Bronchodilator • Plasma theophylline levels should be monitored to keep it in
• MOA: blocks the action of neurotransmitter acetylcholine at the therapeutic range, usually 5-15 µg/ml. Dosage should be
vagal mediated receptor sites adjusted to keep theophylline levels below 20 µg/ml
• Used for maintenance therapy of bronchoconstriction • If patients miss a dose, the following dose should not be
associated with asthma, chronic bronchitis & emphysema doubled
• Blocks the action of acetylcholine in bronchial smooth • Instruct the patient that sustained-release formulations
muscle, this reduces intracellular GMP (bronchoconstrictive should be swallowed intact
substance) • Caution patients in consuming caffeine containing-
• guanosine monophosphate (GMP) beverages and other sources of caffeine. Caffeine can
intensify the adverse effects and decrease the metabolism
Drug Formulation Dosage of theophylline
Adult Child
Inhaler 20 20-80 mcg 20-40 mcg three C. CORTICOSTEROIDS
Ipratropium mcg/dose three to four to four times a • Used for prophylaxis of chronic asthma
(MDI) times a day day (≥8 yrs) • Suppressing inflammation
Not o Decrease synthesis & release of inflammatory
Inhaler 18 recommended in mediators
Tiotropium 18 mcg daily
mcg/dose children and o Decrease infiltration & activity of inflammatory cells
adolescents o Decrease edema of the airway mucosa
o Decrease airway mucus production
Ipratropium bromide (Atrovent) Intranasal Corticosteroids
• Administered by AEROSOL • Most effective for treatment of seasonal and perennial
• ONSET 15 mins; PEAK 1-2 hrs; DURATION 3-4 hrs allergic rhinitis
• Have Anti-inflammatory actions and can prevent or
suppress all major symptoms of allergic rhinitis including
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 congestion, rhinorrhea, sneezing, nasal itching and • Acute attacks of asthma should be treated with short
erythema courses of oral corticosteroids, starting with a high dose for
a few days
Drug Formulation Dosage Adverse Effects:
Adult Child • Mild
1 spray in • Most common effects are drying of nasal mucosa &
each nostril sensations of burning or itching
Nasal Spray
50 mcg /
four times 4-6 sprays / • Candidiasis of the mouth or throat
dose
daily day • Hoarseness
Max. 10 • Can slow growth in children
sprays / day • Adrenal suppression may occur in long-term, high dose
Beclomethasone 2 therapy
Dipropionate applications Same as adult • Increases the risk of cataracts
into each (>6 yrs)
Nasal Spray
nostril twice Not Adrenal insufficiency (A/E of steroids)
50 mcg dose
to four times recommended
(Aqueous)
daily in children
Max. 400 <6yrs
mcg daily
1-2 sprays
into each
Nasal Spray nostril twice Not
50 mcg / daily; after recommended
dose 2-3days: 1 for age 12 yrs
(Aqueous) spray into or below
each nostril
twice daily
Budesonide 400 mcg in
the morning
given as 2
Turbuhaler applications
100mcg / then reduce -
dose to the
smallest
amount
necessary
Nasal Spray
50 mcg / 2 sprays into 1 spray into
dose each nostril each nostril in
(Aqueous) in the the morning
Fluticasone
Nasal Spray morning (4-11yrs)
50 mcg / Max: 8 Max: 4 Corticosteroids
dose sprays/day sprays/day • Rinse mouth with water without swallowing after
(Aqueous) administration to reduce the risk of candidiasis
2 sprays in • If taking bronchodilators by inhalation, use bronchodilators
each nostril several minutes before the corticosteroid to enhance
once daily; application of the corticosteroid into the bronchial tract
1 spray in
Nasal Spray 1spray in
each nostril
Mometasone 50 mcg / each nostril Combination Products
once daily
dose as • Anticholinergic + β2 agonist
(3-11yrs)
maintenance o Combivent (20mcg Ipratropium & 100mcg salbutamol
Max: 8 /dose, MDI)
sprays/day • Corticosteroid + Long-acting β2 agonist
Inhaler o Symbicort (160mcg Budesonide+4.5mcg Formoterol /
25mcg / dose, Turbuhaler)
dose (MDI) o Seretide (Salmeterol + Fluticasone: MDI in Lite,
Inhaler 50 Medium, Forte preparation & Accuhaler)
mcg / dose Mast Cells
(MDI) • Found in connective tissue in the body
Inhaler 125 • Directly involved in the asthmatic response d/t extrinsic
mcg / dose factors
(MDI) • Allergens attach themselves to mast cells & basophils =
Inhaler 250 100 – 1000 50-100 mcg antigen/antibody rxn = release of chem. Mediators =
Fluticasone mcg / dose mcg twice twice daily (4- histamine
(MDI) daily 16 yrs)
Inhaler 50 D. CROMOGLYCATES
mcg / dose • Stabilize mast cells & prevent the release of broncho
(Accuhaler) constrictive & inflammatory substances
Inhaler 100 • when mast cells are confronted with allergens & other
mcg / dose stimuli
(Accuhaler) • Only for prophylaxis of acute asthma attacks
Inhaler 250
mcg / dose
(Accuhaler)

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 Drug Formulation Dosage
Adult Child
10 mg four times
Inhaler (1 daily, may be
Same as
mg & increased to six
adult
5mg/dose) to eight times
Cromoglycate
daily
Na
20 mg four times
Nebuliser
daily, may be Same as
solution 10
increased six adult
mg / ml 2 ml
times daily
Nedocromil Sames as
Inhaler 2 mg 4 mg two to four
Sodium adult (>6
/ dose (MDI) times daily
yrs)

Adverse Effects:
• Transient Bronchospasm - A selective β2 agonist such as
salbutamol or terbutaline may be inhaled a few minutes
beforehand
• Others: coughing, throat irritation

Cromoglycates
• Cromoglycates are for long-term prophylaxis, patients
should administer on a regular schedule & the full
therapeutic effects may take several weeks to develop
• They are contraindicated in patients who are hypersensitive
to the drugs

E. LEUKOTRIENE RECEPTOR ANTAGONISTS

• Act by suppressing the effects of leukotrienes, compounds
that promote bronchoconstriction as well as eosinophil
infiltration, mucus productions, & airway edema
• Help to prevent acute asthma attacks induced by allergens
& other stimuli
• Indicated for long-term treatment of asthma

3 Types:
Decrease bronchoconstriction
• ZAFIRLUKAST administered orally and absorbed rapidly
• ZILEUTON – short t ½; given 4 x day (for adults & children
older than 12 yrs
• MONTELEUKAST- HAS A SHORT HALF LIFE – 2.5-5.5
hours; safe for use of children & 6 yrs and older
Dosage:
• Montelukast (5 & 10 mg tablets)
o Adult: 10 mg daily at bedtime
o Child:
▪ (2-5yrs) 4 mg daily at bedtime
▪ (6-14yrs) 5 mg daily at bedtime

Adverse Effects:
• GI disturbances
• Hypersensitivity reactions
• Restlessness & headache
• Upper respiratory tract infection
• Manufacturer advises to avoid these drugs in pregnancy &
breast-feeding unless essential

IV. MANAGEMENT OF CHRONIC ASTHMA FOR ADULTS

AND SCHOOLCHILD ABOVE 5 YEARS
1. Occasional relief short-acting beta2 agonist
2. Add regular preventer therapy
a. Standard-dose inhaled corticosteroid
3. Add Long-acting inhaled beta2 agonist; dose of inhaled
corticosteroid may also be increased
4. Add high dose of inhaled corticosteroids
5. Add regular oral corticosteroid, e.g., prednisolone
Stepping down:
• Review treatment every 3 months
• If symptoms controlled, may initiate stepwise reduction
o Lowest possible dose oral corticosteroid
o Gradual reduction of dose of inhaled corticosteroid to
the lowest dose which controls asthma